Sensory input to the olfactory bulb (OB) from olfactory receptor neurons is delivered to discrete receptor-specific structures called glomeruli. Different odors activate distinct but overlapping patterns of glomeruli. The overall goal of this proposal is to characterize a neuronal circuit in the OB that could mediate interactions between glomeruli, potentially altering olfactory bulb output. Inter-glomerular connections may support lateral inhibition and excitation;processes that could enhance discrimination between similar odors by increasing the difference in their neuronal representation in the OB. Inter-glomerular connections could also produce temporal patterning in the output cells of the OB and facilitate gain control. The same connections could support both inhibition and excitation, and the polarity of the response may depend on stimulus timing. Therefore, a secondary goal of this proposal is to determine the timing-dependence of inter-glomerular interactions. Aim 1 will identify timing-dependent inhibition between glomeruli with electrophysiological recordings from mitral cells, the output cells of the OB, in rodent OB slices. Aim 2 uses calcium imaging in slices from transgenic animals with fluorescent protein markers for GABAergic cells to test the role of inhibitory periglomerular (PG) cells in lateral inhibition. Aim 2 also tests whether external tufted (ET) or mitral cells are the targets of inhibitory synaptic input through inter-glomerular connections using whole cell recordings from both cell types. Aim 3 tests for timing-dependent inter-glomerular excitation of mitral cells and the function of ET cells in mediating inter-glomerular excitation. This proposal tests a novel model for inter-glomerular interactions in which ET cells mediate both inhibition and excitation. PUBLIC HEALTH RELEVANCE: These studies will contribute to an increased understanding of both normal and disordered olfactory processing. They will characterize an olfactory circuit about which little is known as well as provide insight into the circuits affected by Alzheimer's and Parkinson's diseases. Olfactory dysfunction is one of the earliest symptoms of these disorders;so learning how they affect olfactory circuits could be key for designing better diagnostic tools and halting disease progression. )